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  • 1
    Publication Date: 2012-07-27
    Description: Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4alpha. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kappaB signalling in Group 4, suggest future avenues for rational, targeted therapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683624/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683624/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Northcott, Paul A -- Shih, David J H -- Peacock, John -- Garzia, Livia -- Morrissy, A Sorana -- Zichner, Thomas -- Stutz, Adrian M -- Korshunov, Andrey -- Reimand, Juri -- Schumacher, Steven E -- Beroukhim, Rameen -- Ellison, David W -- Marshall, Christian R -- Lionel, Anath C -- Mack, Stephen -- Dubuc, Adrian -- Yao, Yuan -- Ramaswamy, Vijay -- Luu, Betty -- Rolider, Adi -- Cavalli, Florence M G -- Wang, Xin -- Remke, Marc -- Wu, Xiaochong -- Chiu, Readman Y B -- Chu, Andy -- Chuah, Eric -- Corbett, Richard D -- Hoad, Gemma R -- Jackman, Shaun D -- Li, Yisu -- Lo, Allan -- Mungall, Karen L -- Nip, Ka Ming -- Qian, Jenny Q -- Raymond, Anthony G J -- Thiessen, Nina T -- Varhol, Richard J -- Birol, Inanc -- Moore, Richard A -- Mungall, Andrew J -- Holt, Robert -- Kawauchi, Daisuke -- Roussel, Martine F -- Kool, Marcel -- Jones, David T W -- Witt, Hendrick -- Fernandez-L, Africa -- Kenney, Anna M -- Wechsler-Reya, Robert J -- Dirks, Peter -- Aviv, Tzvi -- Grajkowska, Wieslawa A -- Perek-Polnik, Marta -- Haberler, Christine C -- Delattre, Olivier -- Reynaud, Stephanie S -- Doz, Francois F -- Pernet-Fattet, Sarah S -- Cho, Byung-Kyu -- Kim, Seung-Ki -- Wang, Kyu-Chang -- Scheurlen, Wolfram -- Eberhart, Charles G -- Fevre-Montange, Michelle -- Jouvet, Anne -- Pollack, Ian F -- Fan, Xing -- Muraszko, Karin M -- Gillespie, G Yancey -- Di Rocco, Concezio -- Massimi, Luca -- Michiels, Erna M C -- Kloosterhof, Nanne K -- French, Pim J -- Kros, Johan M -- Olson, James M -- Ellenbogen, Richard G -- Zitterbart, Karel -- Kren, Leos -- Thompson, Reid C -- Cooper, Michael K -- Lach, Boleslaw -- McLendon, Roger E -- Bigner, Darell D -- Fontebasso, Adam -- Albrecht, Steffen -- Jabado, Nada -- Lindsey, Janet C -- Bailey, Simon -- Gupta, Nalin -- Weiss, William A -- Bognar, Laszlo -- Klekner, Almos -- Van Meter, Timothy E -- Kumabe, Toshihiro -- Tominaga, Teiji -- Elbabaa, Samer K -- Leonard, Jeffrey R -- Rubin, Joshua B -- Liau, Linda M -- Van Meir, Erwin G -- Fouladi, Maryam -- Nakamura, Hideo -- Cinalli, Giuseppe -- Garami, Miklos -- Hauser, Peter -- Saad, Ali G -- Iolascon, Achille -- Jung, Shin -- Carlotti, Carlos G -- Vibhakar, Rajeev -- Ra, Young Shin -- Robinson, Shenandoah -- Zollo, Massimo -- Faria, Claudia C -- Chan, Jennifer A -- Levy, Michael L -- Sorensen, Poul H B -- Meyerson, Matthew -- Pomeroy, Scott L -- Cho, Yoon-Jae -- Bader, Gary D -- Tabori, Uri -- Hawkins, Cynthia E -- Bouffet, Eric -- Scherer, Stephen W -- Rutka, James T -- Malkin, David -- Clifford, Steven C -- Jones, Steven J M -- Korbel, Jan O -- Pfister, Stefan M -- Marra, Marco A -- Taylor, Michael D -- AT1-112286/Canadian Institutes of Health Research/Canada -- CA116804/CA/NCI NIH HHS/ -- CA138292/CA/NCI NIH HHS/ -- CA159859/CA/NCI NIH HHS/ -- CA86335/CA/NCI NIH HHS/ -- K08 NS059790/NS/NINDS NIH HHS/ -- P20 CA151129/CA/NCI NIH HHS/ -- P30 CA138292/CA/NCI NIH HHS/ -- P30 HD018655/HD/NICHD NIH HHS/ -- P41 GM103504/GM/NIGMS NIH HHS/ -- R01 CA086335/CA/NCI NIH HHS/ -- R01 CA109467/CA/NCI NIH HHS/ -- R01 CA114567/CA/NCI NIH HHS/ -- R01 CA116804/CA/NCI NIH HHS/ -- R01 CA148621/CA/NCI NIH HHS/ -- R01 CA155360/CA/NCI NIH HHS/ -- R01 CA159859/CA/NCI NIH HHS/ -- R01 CA163737/CA/NCI NIH HHS/ -- R01 NS061070/NS/NINDS NIH HHS/ -- England -- Nature. 2012 Aug 2;488(7409):49-56. doi: 10.1038/nature11327.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22832581" target="_blank"〉PubMed〈/a〉
    Keywords: Carrier Proteins/genetics ; Cerebellar Neoplasms/*classification/*genetics/metabolism ; Child ; DNA Copy Number Variations/genetics ; Gene Duplication/genetics ; Genes, myc/genetics ; Genome, Human/*genetics ; Genomic Structural Variation/*genetics ; Genomics ; Hedgehog Proteins/metabolism ; Humans ; Medulloblastoma/*classification/*genetics/metabolism ; NF-kappa B/metabolism ; Nerve Tissue Proteins/genetics ; Oncogene Proteins, Fusion/genetics ; Proteins/genetics ; RNA, Long Noncoding ; Signal Transduction ; Transforming Growth Factor beta/metabolism ; Translocation, Genetic/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2016-01-14
    Description: The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (〈5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (〈12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morrissy, A Sorana -- Garzia, Livia -- Shih, David J H -- Zuyderduyn, Scott -- Huang, Xi -- Skowron, Patryk -- Remke, Marc -- Cavalli, Florence M G -- Ramaswamy, Vijay -- Lindsay, Patricia E -- Jelveh, Salomeh -- Donovan, Laura K -- Wang, Xin -- Luu, Betty -- Zayne, Kory -- Li, Yisu -- Mayoh, Chelsea -- Thiessen, Nina -- Mercier, Eloi -- Mungall, Karen L -- Ma, Yusanne -- Tse, Kane -- Zeng, Thomas -- Shumansky, Karey -- Roth, Andrew J L -- Shah, Sohrab -- Farooq, Hamza -- Kijima, Noriyuki -- Holgado, Borja L -- Lee, John J Y -- Matan-Lithwick, Stuart -- Liu, Jessica -- Mack, Stephen C -- Manno, Alex -- Michealraj, K A -- Nor, Carolina -- Peacock, John -- Qin, Lei -- Reimand, Juri -- Rolider, Adi -- Thompson, Yuan Y -- Wu, Xiaochong -- Pugh, Trevor -- Ally, Adrian -- Bilenky, Mikhail -- Butterfield, Yaron S N -- Carlsen, Rebecca -- Cheng, Young -- Chuah, Eric -- Corbett, Richard D -- Dhalla, Noreen -- He, An -- Lee, Darlene -- Li, Haiyan I -- Long, William -- Mayo, Michael -- Plettner, Patrick -- Qian, Jenny Q -- Schein, Jacqueline E -- Tam, Angela -- Wong, Tina -- Birol, Inanc -- Zhao, Yongjun -- Faria, Claudia C -- Pimentel, Jose -- Nunes, Sofia -- Shalaby, Tarek -- Grotzer, Michael -- Pollack, Ian F -- Hamilton, Ronald L -- Li, Xiao-Nan -- Bendel, Anne E -- Fults, Daniel W -- Walter, Andrew W -- Kumabe, Toshihiro -- Tominaga, Teiji -- Collins, V Peter -- Cho, Yoon-Jae -- Hoffman, Caitlin -- Lyden, David -- Wisoff, Jeffrey H -- Garvin, James H Jr -- Stearns, Duncan S -- Massimi, Luca -- Schuller, Ulrich -- Sterba, Jaroslav -- Zitterbart, Karel -- Puget, Stephanie -- Ayrault, Olivier -- Dunn, Sandra E -- Tirapelli, Daniela P C -- Carlotti, Carlos G -- Wheeler, Helen -- Hallahan, Andrew R -- Ingram, Wendy -- MacDonald, Tobey J -- Olson, Jeffrey J -- Van Meir, Erwin G -- Lee, Ji-Yeoun -- Wang, Kyu-Chang -- Kim, Seung-Ki -- Cho, Byung-Kyu -- Pietsch, Torsten -- Fleischhack, Gudrun -- Tippelt, Stephan -- Ra, Young Shin -- Bailey, Simon -- Lindsey, Janet C -- Clifford, Steven C -- Eberhart, Charles G -- Cooper, Michael K -- Packer, Roger J -- Massimino, Maura -- Garre, Maria Luisa -- Bartels, Ute -- Tabori, Uri -- Hawkins, Cynthia E -- Dirks, Peter -- Bouffet, Eric -- Rutka, James T -- Wechsler-Reya, Robert J -- Weiss, William A -- Collier, Lara S -- Dupuy, Adam J -- Korshunov, Andrey -- Jones, David T W -- Kool, Marcel -- Northcott, Paul A -- Pfister, Stefan M -- Largaespada, David A -- Mungall, Andrew J -- Moore, Richard A -- Jabado, Nada -- Bader, Gary D -- Jones, Steven J M -- Malkin, David -- Marra, Marco A -- Taylor, Michael D -- R01 CA163722/CA/NCI NIH HHS/ -- R01 NS096236/NS/NINDS NIH HHS/ -- R01CA148699/CA/NCI NIH HHS/ -- R01CA159859/CA/NCI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2016 Jan 21;529(7586):351-7. doi: 10.1038/nature16478. Epub 2016 Jan 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada. ; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada. ; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 0A4, Canada. ; The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada. ; Department of Pediatric Oncology, Hematology, and Clinical Immunology, University Hospital Dusseldorf, M5S 3E1, Germany. ; Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario M5S 3E1, Canada. ; Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 2M9, Canada. ; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 2M9, Canada. ; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada. ; Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada. ; Center for Stem Cell &Regenerative Medicine, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. ; Clinical Genomics Research Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario 44195, Canada. ; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada. ; School of Computing Science, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada. ; Division of Neurosurgery, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisbon 1649-035, Portugal. ; Divison of Pathology, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisbon 1649-035, Portugal. ; Unidade de Neuro-Oncologia Pediatrica, Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Lisbon 1099-023, Portugal. ; Departments of Oncology and Neuro-Oncology, University Children's Hospital of Zurich, Zurich 8032, Switzerland. ; Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224, USA. ; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. ; Brain Tumor Program, Children's Cancer Center and Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA. ; Pediatric Hematology-Oncology, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota 55404, USA. ; Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah 84132, USA. ; A I duPont Hospital for Children, Wilmington, Delaware 19803, USA. ; Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan. ; Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan. ; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK. ; Departments of Neurosurgery, Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA. ; Departments of Pediatrics, Cell &Developmental Biology, Weill Medical College of Cornell University, New York, New York 10065, USA. ; Department of Neurosurgery, NYU Langone Medical Center, New York, New York 10016, USA. ; Department of Pediatrics, Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Columbia University, New York, New York 10032, USA. ; Department of Pediatrics-Hematology and Oncology, Rainbow Babies &Children's Hospital and Department of Pediatrics-Hematology and Oncology, Case Western Reserve, Cleveland, Ohio 44106, USA. ; Pediatric Neurosurgery, Catholic University Medical School, Rome 00198, Italy. ; Center for Neuropathology, Ludwig-Maximilians-Universitat, Munich 81377, Germany. ; Department of Pediatric Oncology, School of Medicine, Masaryk University, Brno 625 00, Czech Republic. ; AP-HP, Department of Neurosurgery, Necker-Enfants Malades Hospital, Universite Rene Descartes, Paris 75743, France. ; Signaling in Development and Brain Tumors, CNRS UMR 3347 / INSERM U1021, Institut Curie, Paris Cedex 5 91405, France. ; Division of Hematology/Oncology, British Columbia Children's Hospital, Vancouver, British Columbia V6H 3V4, Canada. ; Department of Surgery and Anatomy, Faculty of Medicine of Ribeirao Preto, Universidade de Sao Paulo, Brazil, Rebeirao Preto, Sao Paulo 14049-900, Brazil. ; Kolling Institute of Medical Research, The University of Sydney, Sydney, New South Wales 2065, Australia. ; Queensland Children's Medical Research Institute, Children's Health Queensland, Brisbane, Queensland 4029, Australia. ; Division of Oncology, Children's Health Queensland, Brisbane, Queensland 4029, Australia. ; UQ Child Health Research Centre, The University of Queensland, Brisbane 4029, Australia. ; Pediatric Neuro-Oncology Program, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia 30307, USA. ; Department of Neurosurgery, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA. ; Department of Hematology &Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA. ; Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul 30322, South Korea. ; Institute for Neuropathology, University of Bonn D-53105, Germany. ; Children's University Hospital of Essen D-45147, Germany. ; Department of Neurosurgery, University of Ulsan, Asan Medical Center, Seoul 05505, South Korea. ; Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE1 4LP, UK. ; Departments of Pathology, Ophthalmology and Oncology, John Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; Department of Neurology, Vanderbilt Medical Center, Nashville, Tennessee 37232-8550, USA. ; Department of Neurology, Children's National Medical Center, Washington DC 20010-2970, USA. ; Fondazione IRCCS Istituto Nazionale Tumori, Milan 20133, Italy. ; U.O. Neurochirurgia, Istituto Giannina Gaslini, Genova 16147, Italy. ; Department of Haematology &Oncology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. ; Division of Pathology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. ; Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA. ; Departments of Pediatrics, Neurology and Neurosurgery, University of California San Francisco, San Francisco, California 94158, USA. ; School of Pharmacology, University of Wisconsin, Madison, Wisconsin 53715, USA. ; Molecular &Cellular Biology Program, University of Iowa, Iowa City, Iowa 52242, USA. ; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. ; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. ; Department of Pediatric Oncology, University Hospital Heidelberg, Heidelberg 69120, Germany. ; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA. ; Division of Hematology/Oncology, McGill University, Montreal, Quebec H2W 1S6., Canada. ; McLaughlin Centre and Department of Molecular Genetics, Banting and Best Department of Medical Research and Samuel Lunenfeld Research Institute at Mount Sinai Hospital, University of Toronto, Toronto, Ontario M5G 1L7, Canada. ; Department of Molecular Biology &Biochemistry, Simon Fraser University, Burnaby, British Columbia M5G 1L7, Canada. ; Department of Pediatrics, University of Toronto, Toronto, Ontario M5G 1X8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26760213" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2012-12-01
    Description: Placental development and genomic imprinting coevolved with parental conflict over resource distribution to mammalian offspring. The imprinted genes IGF2 and IGF2R code for the growth promoter insulin-like growth factor 2 (IGF2) and its inhibitor, mannose 6-phosphate (M6P)/IGF2 receptor (IGF2R), respectively. M6P/IGF2R of birds and fish do not recognize IGF2. In monotremes, which lack imprinting, IGF2 specifically bound M6P/IGF2R via a hydrophobic CD loop. We show that the DNA coding the CD loop in monotremes functions as an exon splice enhancer (ESE) and that structural evolution of binding site loops (AB, HI, FG) improved therian IGF2 affinity. We propose that ESE evolution led to the fortuitous acquisition of IGF2 binding by M6P/IGF2R that drew IGF2R into parental conflict; subsequent imprinting may then have accelerated affinity maturation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658703/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658703/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Williams, Christopher -- Hoppe, Hans-Jurgen -- Rezgui, Dellel -- Strickland, Madeleine -- Forbes, Briony E -- Grutzner, Frank -- Frago, Susana -- Ellis, Rosamund Z -- Wattana-Amorn, Pakorn -- Prince, Stuart N -- Zaccheo, Oliver J -- Nolan, Catherine M -- Mungall, Andrew J -- Jones, E Yvonne -- Crump, Matthew P -- Hassan, A Bassim -- 082352/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 9891/Cancer Research UK/United Kingdom -- A13295/Cancer Research UK/United Kingdom -- A9891/Cancer Research UK/United Kingdom -- C375/Cancer Research UK/United Kingdom -- C429/Cancer Research UK/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2012 Nov 30;338(6111):1209-13. doi: 10.1126/science.1228633.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Organic and Biological Chemistry, School of Chemistry, University of Bristol, Bristol BS8 1TS, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23197533" target="_blank"〉PubMed〈/a〉
    Keywords: *Alternative Splicing ; Amino Acid Sequence ; Animals ; Binding Sites/genetics ; Conserved Sequence ; Enhancer Elements, Genetic/*genetics ; *Evolution, Molecular ; *Exons ; Genomic Imprinting ; Humans ; Insulin-Like Growth Factor II/*chemistry/classification/genetics ; Molecular Sequence Data ; Phylogeny ; Protein Structure, Tertiary ; Receptor, IGF Type 2/*chemistry/classification/genetics ; Species Specificity
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2014-12-04
    Description: Human cancers, including breast cancers, comprise clones differing in mutation content. Clones evolve dynamically in space and time following principles of Darwinian evolution, underpinning important emergent features such as drug resistance and metastasis. Human breast cancer xenoengraftment is used as a means of capturing and studying tumour biology, and breast tumour xenografts are generally assumed to be reasonable models of the originating tumours. However, the consequences and reproducibility of engraftment and propagation on the genomic clonal architecture of tumours have not been systematically examined at single-cell resolution. Here we show, using deep-genome and single-cell sequencing methods, the clonal dynamics of initial engraftment and subsequent serial propagation of primary and metastatic human breast cancers in immunodeficient mice. In all 15 cases examined, clonal selection on engraftment was observed in both primary and metastatic breast tumours, varying in degree from extreme selective engraftment of minor (〈5% of starting population) clones to moderate, polyclonal engraftment. Furthermore, ongoing clonal dynamics during serial passaging is a feature of tumours experiencing modest initial selection. Through single-cell sequencing, we show that major mutation clusters estimated from tumour population sequencing relate predictably to the most abundant clonal genotypes, even in clonally complex and rapidly evolving cases. Finally, we show that similar clonal expansion patterns can emerge in independent grafts of the same starting tumour population, indicating that genomic aberrations can be reproducible determinants of evolutionary trajectories. Our results show that measurement of genomically defined clonal population dynamics will be highly informative for functional studies using patient-derived breast cancer xenoengraftment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eirew, Peter -- Steif, Adi -- Khattra, Jaswinder -- Ha, Gavin -- Yap, Damian -- Farahani, Hossein -- Gelmon, Karen -- Chia, Stephen -- Mar, Colin -- Wan, Adrian -- Laks, Emma -- Biele, Justina -- Shumansky, Karey -- Rosner, Jamie -- McPherson, Andrew -- Nielsen, Cydney -- Roth, Andrew J L -- Lefebvre, Calvin -- Bashashati, Ali -- de Souza, Camila -- Siu, Celia -- Aniba, Radhouane -- Brimhall, Jazmine -- Oloumi, Arusha -- Osako, Tomo -- Bruna, Alejandra -- Sandoval, Jose L -- Algara, Teresa -- Greenwood, Wendy -- Leung, Kaston -- Cheng, Hongwei -- Xue, Hui -- Wang, Yuzhuo -- Lin, Dong -- Mungall, Andrew J -- Moore, Richard -- Zhao, Yongjun -- Lorette, Julie -- Nguyen, Long -- Huntsman, David -- Eaves, Connie J -- Hansen, Carl -- Marra, Marco A -- Caldas, Carlos -- Shah, Sohrab P -- Aparicio, Samuel -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2015 Feb 19;518(7539):422-6. doi: 10.1038/nature13952. Epub 2014 Nov 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada [2] Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada. ; Department of Medical Oncology, BC Cancer Agency, 600 West 10th Avenue, Vancouver, British Columbia V5Z 4E6, Canada. ; Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. ; 1] Department of Oncology, University of Cambridge, Hills Road, Cambridge CB2 2XZ, UK [2] Cancer Research UK Cambridge Research Institute, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE, UK. ; 1] Centre for High-Throughput Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada [2] Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada. ; 1] Department of Experimental Therapeutics, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada [2] The Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia V5Z 1M9, Canada. ; Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada. ; Centre for Translational and Applied Genomics, BC Cancer Agency, 600 West 10th Avenue, Vancouver, British Columbia V5Z 4E6, Canada. ; 1] Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada [2] Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada. ; 1] Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada [2] Centre for Translational and Applied Genomics, BC Cancer Agency, 600 West 10th Avenue, Vancouver, British Columbia V5Z 4E6, Canada. ; 1] Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada [2] Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada [3] Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada. ; 1] Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada [2] Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada [3] Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada [4] Centre for Translational and Applied Genomics, BC Cancer Agency, 600 West 10th Avenue, Vancouver, British Columbia V5Z 4E6, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470049" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/*genetics/*pathology/secondary ; Clone Cells/*metabolism/*pathology ; DNA Mutational Analysis ; Genome, Human/*genetics ; Genomics ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; Mice ; Neoplasm Transplantation ; *Single-Cell Analysis ; Time Factors ; Transplantation, Heterologous ; *Xenograft Model Antitumor Assays/methods
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2011-07-29
    Description: Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210554/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210554/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morin, Ryan D -- Mendez-Lago, Maria -- Mungall, Andrew J -- Goya, Rodrigo -- Mungall, Karen L -- Corbett, Richard D -- Johnson, Nathalie A -- Severson, Tesa M -- Chiu, Readman -- Field, Matthew -- Jackman, Shaun -- Krzywinski, Martin -- Scott, David W -- Trinh, Diane L -- Tamura-Wells, Jessica -- Li, Sa -- Firme, Marlo R -- Rogic, Sanja -- Griffith, Malachi -- Chan, Susanna -- Yakovenko, Oleksandr -- Meyer, Irmtraud M -- Zhao, Eric Y -- Smailus, Duane -- Moksa, Michelle -- Chittaranjan, Suganthi -- Rimsza, Lisa -- Brooks-Wilson, Angela -- Spinelli, John J -- Ben-Neriah, Susana -- Meissner, Barbara -- Woolcock, Bruce -- Boyle, Merrill -- McDonald, Helen -- Tam, Angela -- Zhao, Yongjun -- Delaney, Allen -- Zeng, Thomas -- Tse, Kane -- Butterfield, Yaron -- Birol, Inanc -- Holt, Rob -- Schein, Jacqueline -- Horsman, Douglas E -- Moore, Richard -- Jones, Steven J M -- Connors, Joseph M -- Hirst, Martin -- Gascoyne, Randy D -- Marra, Marco A -- 1U01CA114778/CA/NCI NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- P50CA130805-01/CA/NCI NIH HHS/ -- TGT-53912/Canadian Institutes of Health Research/Canada -- U24 CA143866/CA/NCI NIH HHS/ -- U24 CA143866-01/CA/NCI NIH HHS/ -- U24 CA143866-02/CA/NCI NIH HHS/ -- U24 CA143866-03/CA/NCI NIH HHS/ -- England -- Nature. 2011 Jul 27;476(7360):298-303. doi: 10.1038/nature10351.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21796119" target="_blank"〉PubMed〈/a〉
    Keywords: Chromatin/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Genome, Human/genetics ; Histone Acetyltransferases/genetics/metabolism ; Histone-Lysine N-Methyltransferase/genetics/metabolism ; Histones/*metabolism ; Humans ; Loss of Heterozygosity/genetics ; Lymphoma, Follicular/enzymology/genetics ; Lymphoma, Large B-Cell, Diffuse/enzymology/genetics ; Lymphoma, Non-Hodgkin/enzymology/*genetics ; MADS Domain Proteins/genetics/metabolism ; MEF2 Transcription Factors ; Mutation/*genetics ; Myogenic Regulatory Factors/genetics/metabolism ; Neoplasm Proteins/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2018-04-11
    Description: Erratum: The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions Erratum: The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions, Published online: 10 April 2018; doi:10.1038/nm0418-526b Erratum: The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions
    Print ISSN: 1078-8956
    Electronic ISSN: 1546-170X
    Topics: Biology , Medicine
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  • 7
    Publication Date: 2014-03-29
    Description: Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that enhancers share properties with CpG-poor messenger RNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous enhancers. We further explore the utility of enhancer redundancy, which explains gene expression strength rather than expression patterns. The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Andersson, Robin -- Gebhard, Claudia -- Miguel-Escalada, Irene -- Hoof, Ilka -- Bornholdt, Jette -- Boyd, Mette -- Chen, Yun -- Zhao, Xiaobei -- Schmidl, Christian -- Suzuki, Takahiro -- Ntini, Evgenia -- Arner, Erik -- Valen, Eivind -- Li, Kang -- Schwarzfischer, Lucia -- Glatz, Dagmar -- Raithel, Johanna -- Lilje, Berit -- Rapin, Nicolas -- Bagger, Frederik Otzen -- Jorgensen, Mette -- Andersen, Peter Refsing -- Bertin, Nicolas -- Rackham, Owen -- Burroughs, A Maxwell -- Baillie, J Kenneth -- Ishizu, Yuri -- Shimizu, Yuri -- Furuhata, Erina -- Maeda, Shiori -- Negishi, Yutaka -- Mungall, Christopher J -- Meehan, Terrence F -- Lassmann, Timo -- Itoh, Masayoshi -- Kawaji, Hideya -- Kondo, Naoto -- Kawai, Jun -- Lennartsson, Andreas -- Daub, Carsten O -- Heutink, Peter -- Hume, David A -- Jensen, Torben Heick -- Suzuki, Harukazu -- Hayashizaki, Yoshihide -- Muller, Ferenc -- FANTOM Consortium -- Forrest, Alistair R R -- Carninci, Piero -- Rehli, Michael -- Sandelin, Albin -- MC_PC_U127597124/Medical Research Council/United Kingdom -- MC_UP_1102/1/Medical Research Council/United Kingdom -- R01 DE022969/DE/NIDCR NIH HHS/ -- England -- Nature. 2014 Mar 27;507(7493):455-61. doi: 10.1038/nature12787.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark [2]. ; 1] Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany [2] Regensburg Centre for Interventional Immunology (RCI), D-93042 Regensburg, Germany [3]. ; School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. ; The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark. ; 1] The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark [2] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany. ; 1] RIKEN OMICS Science Centre, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [2] RIKEN Center for Life Science Technologies (Division of Genomic Technologies), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan. ; Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, C.F. Mollers Alle 3, Building 1130, DK-8000 Aarhus, Denmark. ; 1] The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark [2] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; 1] The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark [2] The Finsen Laboratory, Rigshospitalet and Danish Stem Cell Centre (DanStem), University of Copenhagen, Ole Maaloes Vej 5, DK-2200, Denmark. ; Roslin Institute, Edinburgh University, Easter Bush, Midlothian, Edinburgh EH25 9RG, UK. ; Genomics Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road MS 64-121, Berkeley, California 94720, USA. ; EMBL Outstation - Hinxton, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; 1] RIKEN OMICS Science Centre, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [2] RIKEN Center for Life Science Technologies (Division of Genomic Technologies), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [3] RIKEN Preventive Medicine and Diagnosis Innovation Program, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan. ; 1] RIKEN OMICS Science Centre, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [2] RIKEN Preventive Medicine and Diagnosis Innovation Program, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan. ; Department of Biosciences and Nutrition, Karolinska Institutet, Halsovagen 7, SE-4183 Huddinge, Stockholm, Sweden. ; 1] RIKEN OMICS Science Centre, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [2] RIKEN Center for Life Science Technologies (Division of Genomic Technologies), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [3] Department of Biosciences and Nutrition, Karolinska Institutet, Halsovagen 7, SE-4183 Huddinge, Stockholm, Sweden. ; Department of Clinical Genetics, VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, Netherlands. ; 1] Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany [2] Regensburg Centre for Interventional Immunology (RCI), D-93042 Regensburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670763" target="_blank"〉PubMed〈/a〉
    Keywords: *Atlases as Topic ; Cell Line ; Cells, Cultured ; Cluster Analysis ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation/*genetics ; Genetic Predisposition to Disease/genetics ; HeLa Cells ; Humans ; *Molecular Sequence Annotation ; *Organ Specificity ; Polymorphism, Single Nucleotide/genetics ; Promoter Regions, Genetic/genetics ; RNA, Messenger/biosynthesis/genetics ; Transcription Initiation Site ; Transcription Initiation, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2014-03-29
    Description: Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529748/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉FANTOM Consortium and the RIKEN PMI and CLST (DGT) -- Forrest, Alistair R R -- Kawaji, Hideya -- Rehli, Michael -- Baillie, J Kenneth -- de Hoon, Michiel J L -- Haberle, Vanja -- Lassmann, Timo -- Kulakovskiy, Ivan V -- Lizio, Marina -- Itoh, Masayoshi -- Andersson, Robin -- Mungall, Christopher J -- Meehan, Terrence F -- Schmeier, Sebastian -- Bertin, Nicolas -- Jorgensen, Mette -- Dimont, Emmanuel -- Arner, Erik -- Schmidl, Christian -- Schaefer, Ulf -- Medvedeva, Yulia A -- Plessy, Charles -- Vitezic, Morana -- Severin, Jessica -- Semple, Colin A -- Ishizu, Yuri -- Young, Robert S -- Francescatto, Margherita -- Alam, Intikhab -- Albanese, Davide -- Altschuler, Gabriel M -- Arakawa, Takahiro -- Archer, John A C -- Arner, Peter -- Babina, Magda -- Rennie, Sarah -- Balwierz, Piotr J -- Beckhouse, Anthony G -- Pradhan-Bhatt, Swati -- Blake, Judith A -- Blumenthal, Antje -- Bodega, Beatrice -- Bonetti, Alessandro -- Briggs, James -- Brombacher, Frank -- Burroughs, A Maxwell -- Califano, Andrea -- Cannistraci, Carlo V -- Carbajo, Daniel -- Chen, Yun -- Chierici, Marco -- Ciani, Yari -- Clevers, Hans C -- Dalla, Emiliano -- Davis, Carrie A -- Detmar, Michael -- Diehl, Alexander D -- Dohi, Taeko -- Drablos, Finn -- Edge, Albert S B -- Edinger, Matthias -- Ekwall, Karl -- Endoh, Mitsuhiro -- Enomoto, Hideki -- Fagiolini, Michela -- Fairbairn, Lynsey -- Fang, Hai -- Farach-Carson, Mary C -- Faulkner, Geoffrey J -- Favorov, Alexander V -- Fisher, Malcolm E -- Frith, Martin C -- Fujita, Rie -- Fukuda, Shiro -- Furlanello, Cesare -- Furino, Masaaki -- Furusawa, Jun-ichi -- Geijtenbeek, Teunis B -- Gibson, Andrew P -- Gingeras, Thomas -- Goldowitz, Daniel -- Gough, Julian -- Guhl, Sven -- Guler, Reto -- Gustincich, Stefano -- Ha, Thomas J -- Hamaguchi, Masahide -- Hara, Mitsuko -- Harbers, Matthias -- Harshbarger, Jayson -- Hasegawa, Akira -- Hasegawa, Yuki -- Hashimoto, Takehiro -- Herlyn, Meenhard -- Hitchens, Kelly J -- Ho Sui, Shannan J -- Hofmann, Oliver M -- Hoof, Ilka -- Hori, Furni -- Huminiecki, Lukasz -- Iida, Kei -- Ikawa, Tomokatsu -- Jankovic, Boris R -- Jia, Hui -- Joshi, Anagha -- Jurman, Giuseppe -- Kaczkowski, Bogumil -- Kai, Chieko -- Kaida, Kaoru -- Kaiho, Ai -- Kajiyama, Kazuhiro -- Kanamori-Katayama, Mutsumi -- Kasianov, Artem S -- Kasukawa, Takeya -- Katayama, Shintaro -- Kato, Sachi -- Kawaguchi, Shuji -- Kawamoto, Hiroshi -- Kawamura, Yuki I -- Kawashima, Tsugumi -- Kempfle, Judith S -- Kenna, Tony J -- Kere, Juha -- Khachigian, Levon M -- Kitamura, Toshio -- Klinken, S Peter -- Knox, Alan J -- Kojima, Miki -- Kojima, Soichi -- Kondo, Naoto -- Koseki, Haruhiko -- Koyasu, Shigeo -- Krampitz, Sarah -- Kubosaki, Atsutaka -- Kwon, Andrew T -- Laros, Jeroen F J -- Lee, Weonju -- Lennartsson, Andreas -- Li, Kang -- Lilje, Berit -- Lipovich, Leonard -- Mackay-Sim, Alan -- Manabe, Ri-ichiroh -- Mar, Jessica C -- Marchand, Benoit -- Mathelier, Anthony -- Mejhert, Niklas -- Meynert, Alison -- Mizuno, Yosuke -- de Lima Morais, David A -- Morikawa, Hiromasa -- Morimoto, Mitsuru -- Moro, Kazuyo -- Motakis, Efthymios -- Motohashi, Hozumi -- Mummery, Christine L -- Murata, Mitsuyoshi -- Nagao-Sato, Sayaka -- Nakachi, Yutaka -- Nakahara, Fumio -- Nakamura, Toshiyuki -- Nakamura, Yukio -- Nakazato, Kenichi -- van Nimwegen, Erik -- Ninomiya, Noriko -- Nishiyori, Hiromi -- Noma, Shohei -- Noazaki, Tadasuke -- Ogishima, Soichi -- Ohkura, Naganari -- Ohimiya, Hiroko -- Ohno, Hiroshi -- Ohshima, Mitsuhiro -- Okada-Hatakeyama, Mariko -- Okazaki, Yasushi -- Orlando, Valerio -- Ovchinnikov, Dmitry A -- Pain, Arnab -- Passier, Robert -- Patrikakis, Margaret -- Persson, Helena -- Piazza, Silvano -- Prendergast, James G D -- Rackham, Owen J L -- Ramilowski, Jordan A -- Rashid, Mamoon -- Ravasi, Timothy -- Rizzu, Patrizia -- Roncador, Marco -- Roy, Sugata -- Rye, Morten B -- Saijyo, Eri -- Sajantila, Antti -- Saka, Akiko -- Sakaguchi, Shimon -- Sakai, Mizuho -- Sato, Hiroki -- Savvi, Suzana -- Saxena, Alka -- Schneider, Claudio -- Schultes, Erik A -- Schulze-Tanzil, Gundula G -- Schwegmann, Anita -- Sengstag, Thierry -- Sheng, Guojun -- Shimoji, Hisashi -- Shimoni, Yishai -- Shin, Jay W -- Simon, Christophe -- Sugiyama, Daisuke -- Sugiyama, Takaai -- Suzuki, Masanori -- Suzuki, Naoko -- Swoboda, Rolf K -- 't Hoen, Peter A C -- Tagami, Michihira -- Takahashi, Naoko -- Takai, Jun -- Tanaka, Hiroshi -- Tatsukawa, Hideki -- Tatum, Zuotian -- Thompson, Mark -- Toyodo, Hiroo -- Toyoda, Tetsuro -- Valen, Elvind -- van de Wetering, Marc -- van den Berg, Linda M -- Verado, Roberto -- Vijayan, Dipti -- Vorontsov, Ilya E -- Wasserman, Wyeth W -- Watanabe, Shoko -- Wells, Christine A -- Winteringham, Louise N -- Wolvetang, Ernst -- Wood, Emily J -- Yamaguchi, Yoko -- Yamamoto, Masayuki -- Yoneda, Misako -- Yonekura, Yohei -- Yoshida, Shigehiro -- Zabierowski, Susan E -- Zhang, Peter G -- Zhao, Xiaobei -- Zucchelli, Silvia -- Summers, Kim M -- Suzuki, Harukazu -- Daub, Carsten O -- Kawai, Jun -- Heutink, Peter -- Hide, Winston -- Freeman, Tom C -- Lenhard, Boris -- Bajic, Vladimir B -- Taylor, Martin S -- Makeev, Vsevolod J -- Sandelin, Albin -- Hume, David A -- Carninci, Piero -- Hayashizaki, Yoshihide -- BB/F003722/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G022771/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I001107/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MC_PC_U127597124/Medical Research Council/United Kingdom -- MC_UP_1102/1/Medical Research Council/United Kingdom -- R01 DE022969/DE/NIDCR NIH HHS/ -- R01 GM084875/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Mar 27;507(7493):462-70. doi: 10.1038/nature13182.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670764" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Atlases as Topic ; Cell Line ; Cells, Cultured ; Cluster Analysis ; Conserved Sequence/genetics ; Gene Expression Regulation/genetics ; Gene Regulatory Networks/genetics ; Genes, Essential/genetics ; Genome/genetics ; Humans ; Mice ; *Molecular Sequence Annotation ; Open Reading Frames/genetics ; Organ Specificity ; Promoter Regions, Genetic/*genetics ; RNA, Messenger/analysis/genetics ; Transcription Factors/metabolism ; Transcription Initiation Site ; Transcription, Genetic/genetics ; Transcriptome/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2015-02-20
    Description: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530010/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530010/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roadmap Epigenomics Consortium -- Kundaje, Anshul -- Meuleman, Wouter -- Ernst, Jason -- Bilenky, Misha -- Yen, Angela -- Heravi-Moussavi, Alireza -- Kheradpour, Pouya -- Zhang, Zhizhuo -- Wang, Jianrong -- Ziller, Michael J -- Amin, Viren -- Whitaker, John W -- Schultz, Matthew D -- Ward, Lucas D -- Sarkar, Abhishek -- Quon, Gerald -- Sandstrom, Richard S -- Eaton, Matthew L -- Wu, Yi-Chieh -- Pfenning, Andreas R -- Wang, Xinchen -- Claussnitzer, Melina -- Liu, Yaping -- Coarfa, Cristian -- Harris, R Alan -- Shoresh, Noam -- Epstein, Charles B -- Gjoneska, Elizabeta -- Leung, Danny -- Xie, Wei -- Hawkins, R David -- Lister, Ryan -- Hong, Chibo -- Gascard, Philippe -- Mungall, Andrew J -- Moore, Richard -- Chuah, Eric -- Tam, Angela -- Canfield, Theresa K -- Hansen, R Scott -- Kaul, Rajinder -- Sabo, Peter J -- Bansal, Mukul S -- Carles, Annaick -- Dixon, Jesse R -- Farh, Kai-How -- Feizi, Soheil -- Karlic, Rosa -- Kim, Ah-Ram -- Kulkarni, Ashwinikumar -- Li, Daofeng -- Lowdon, Rebecca -- Elliott, GiNell -- Mercer, Tim R -- Neph, Shane J -- Onuchic, Vitor -- Polak, Paz -- Rajagopal, Nisha -- Ray, Pradipta -- Sallari, Richard C -- Siebenthall, Kyle T -- Sinnott-Armstrong, Nicholas A -- Stevens, Michael -- Thurman, Robert E -- Wu, Jie -- Zhang, Bo -- Zhou, Xin -- Beaudet, Arthur E -- Boyer, Laurie A -- De Jager, Philip L -- Farnham, Peggy J -- Fisher, Susan J -- Haussler, David -- Jones, Steven J M -- Li, Wei -- Marra, Marco A -- McManus, Michael T -- Sunyaev, Shamil -- Thomson, James A -- Tlsty, Thea D -- Tsai, Li-Huei -- Wang, Wei -- Waterland, Robert A -- Zhang, Michael Q -- Chadwick, Lisa H -- Bernstein, Bradley E -- Costello, Joseph F -- Ecker, Joseph R -- Hirst, Martin -- Meissner, Alexander -- Milosavljevic, Aleksandar -- Ren, Bing -- Stamatoyannopoulos, John A -- Wang, Ting -- Kellis, Manolis -- 5R24HD000836/HD/NICHD NIH HHS/ -- ES017166/ES/NIEHS NIH HHS/ -- F32 HL110473/HL/NHLBI NIH HHS/ -- F32HL110473/HL/NHLBI NIH HHS/ -- K99 HL119617/HL/NHLBI NIH HHS/ -- K99HL119617/HL/NHLBI NIH HHS/ -- P01 DA008227/DA/NIDA NIH HHS/ -- P30AG10161/AG/NIA NIH HHS/ -- P50 MH096890/MH/NIMH NIH HHS/ -- R01 AG015819/AG/NIA NIH HHS/ -- R01 AG017917/AG/NIA NIH HHS/ -- R01 ES024984/ES/NIEHS NIH HHS/ -- R01 ES024992/ES/NIEHS NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- R01 HG007175/HG/NHGRI NIH HHS/ -- R01 HG007354/HG/NHGRI NIH HHS/ -- R01AG15819/AG/NIA NIH HHS/ -- R01AG17917/AG/NIA NIH HHS/ -- R01HG004037/HG/NHGRI NIH HHS/ -- R01HG004037-S1/HG/NHGRI NIH HHS/ -- R01NS078839/NS/NINDS NIH HHS/ -- RC1HG005334/HG/NHGRI NIH HHS/ -- RF1 AG015819/AG/NIA NIH HHS/ -- T32 ES007032/ES/NIEHS NIH HHS/ -- T32 GM007198/GM/NIGMS NIH HHS/ -- T32 GM007266/GM/NIGMS NIH HHS/ -- T32 GM081739/GM/NIGMS NIH HHS/ -- U01 ES017154/ES/NIEHS NIH HHS/ -- U01AG46152/AG/NIA NIH HHS/ -- U01DA025956/DA/NIDA NIH HHS/ -- U01ES017154/ES/NIEHS NIH HHS/ -- U01ES017155/ES/NIEHS NIH HHS/ -- U01ES017156/ES/NIEHS NIH HHS/ -- U01ES017166/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Feb 19;518(7539):317-30. doi: 10.1038/nature14248.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [3] Department of Genetics, Department of Computer Science, 300 Pasteur Dr., Lane Building, L301, Stanford, California 94305-5120, USA. ; 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. ; 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [3] Department of Biological Chemistry, University of California, Los Angeles, 615 Charles E Young Dr South, Los Angeles, California 90095, USA. ; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Department of Stem Cell and Regenerative Biology, 7 Divinity Ave, Cambridge, Massachusetts 02138, USA. ; Epigenome Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. ; Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, Moores Cancer Center, Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. ; Genomic Analysis Laboratory, Howard Hughes Medical Institute &The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA. ; Department of Genome Sciences, University of Washington, 3720 15th Ave. NE, Seattle, Washington 98195, USA. ; 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [3] Biology Department, Massachusetts Institute of Technology, 31 Ames St, Cambridge, Massachusetts 02142, USA. ; The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 43 Vassar St, Cambridge, Massachusetts 02139, USA. ; 1] Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, Moores Cancer Center, Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. [2] Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093, USA. ; Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1450 3rd Street, San Francisco, California 94158, USA. ; Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143-0511, USA. ; Department of Medicine, Division of Medical Genetics, University of Washington, 2211 Elliot Avenue, Seattle, Washington 98121, USA. ; 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [3] Department of Computer Science &Engineering, University of Connecticut, 371 Fairfield Way, Storrs, Connecticut 06269, USA. ; Department of Microbiology and Immunology and Centre for High-Throughput Biology, University of British Columbia, 2125 East Mall, Vancouver, British Columbia V6T 1Z4, Canada. ; Bioinformatics Group, Department of Molecular Biology, Division of Biology, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia. ; Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas, Dallas, NSERL, RL10, 800 W Campbell Road, Richardson, Texas 75080, USA. ; Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA. ; Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland 4072, Australia. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Brigham &Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA. ; 1] Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA. [2] Department of Computer Science and Engineeering, Washington University in St. Louis, St. Louis, Missouri 63130, USA. ; 1] Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York 11794-3600, USA. [2] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. ; Molecular and Human Genetics Department, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. ; Biology Department, Massachusetts Institute of Technology, 31 Ames St, Cambridge, Massachusetts 02142, USA. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Brigham &Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA. [3] Harvard Medical School, 25 Shattuck St, Boston, Massachusetts 02115, USA. ; Department of Biochemistry, Keck School of Medicine, University of Southern California, 1450 Biggy Street, Los Angeles, California 90089-9601, USA. ; ObGyn, Reproductive Sciences, University of California San Francisco, 35 Medical Center Way, San Francisco, California 94143, USA. ; Center for Biomolecular Sciences and Engineering, University of Santa Cruz, 1156 High Street, Santa Cruz, California 95064, USA. ; 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. [2] Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5A 1S6, Canada. [3] Department of Medical Genetics, University of British Columbia, 2329 West Mall, Vancouver, BC, Canada, V6T 1Z4. ; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. ; 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. [2] Department of Medical Genetics, University of British Columbia, 2329 West Mall, Vancouver, BC, Canada, V6T 1Z4. ; Department of Microbiology and Immunology, Diabetes Center, University of California, San Francisco, 513 Parnassus Ave, San Francisco, California 94143-0534, USA. ; 1] University of Wisconsin, Madison, Wisconsin 53715, USA. [2] Morgridge Institute for Research, 330 N. Orchard Street, Madison, Wisconsin 53707, USA. ; USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, 1100 Bates Street, Houston, Texas 77030, USA. ; 1] Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas, Dallas, NSERL, RL10, 800 W Campbell Road, Richardson, Texas 75080, USA. [2] Bioinformatics Division, Center for Synthetic and Systems Biology, TNLIST, Tsinghua University, Beijing 100084, China. ; National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park, North Carolina 27709, USA. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Massachusetts General Hospital, 55 Fruit St, Boston, Massachusetts 02114, USA. [3] Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, Maryland 20815-6789, USA. ; 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. [2] Department of Microbiology and Immunology and Centre for High-Throughput Biology, University of British Columbia, 2125 East Mall, Vancouver, British Columbia V6T 1Z4, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25693563" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cell Lineage/genetics ; Cells, Cultured ; Chromatin/chemistry/genetics/metabolism ; Chromosomes, Human/chemistry/genetics/metabolism ; DNA/chemistry/genetics/metabolism ; DNA Methylation ; Datasets as Topic ; Enhancer Elements, Genetic/genetics ; Epigenesis, Genetic/*genetics ; *Epigenomics ; Genetic Variation/genetics ; Genome, Human/*genetics ; Genome-Wide Association Study ; Histones/metabolism ; Humans ; Organ Specificity/genetics ; RNA/genetics ; Reference Values
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2013-12-18
    Description: Tumor recurrence is a leading cause of cancer mortality. Therapies for recurrent disease may fail, at least in part, because the genomic alterations driving the growth of recurrences are distinct from those in the initial tumor. To explore this hypothesis, we sequenced the exomes of 23 initial low-grade gliomas and recurrent tumors resected from the same patients. In 43% of cases, at least half of the mutations in the initial tumor were undetected at recurrence, including driver mutations in TP53, ATRX, SMARCA4, and BRAF; this suggests that recurrent tumors are often seeded by cells derived from the initial tumor at a very early stage of their evolution. Notably, tumors from 6 of 10 patients treated with the chemotherapeutic drug temozolomide (TMZ) followed an alternative evolutionary path to high-grade glioma. At recurrence, these tumors were hypermutated and harbored driver mutations in the RB (retinoblastoma) and Akt-mTOR (mammalian target of rapamycin) pathways that bore the signature of TMZ-induced mutagenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998672/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998672/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, Brett E -- Mazor, Tali -- Hong, Chibo -- Barnes, Michael -- Aihara, Koki -- McLean, Cory Y -- Fouse, Shaun D -- Yamamoto, Shogo -- Ueda, Hiroki -- Tatsuno, Kenji -- Asthana, Saurabh -- Jalbert, Llewellyn E -- Nelson, Sarah J -- Bollen, Andrew W -- Gustafson, W Clay -- Charron, Elise -- Weiss, William A -- Smirnov, Ivan V -- Song, Jun S -- Olshen, Adam B -- Cha, Soonmee -- Zhao, Yongjun -- Moore, Richard A -- Mungall, Andrew J -- Jones, Steven J M -- Hirst, Martin -- Marra, Marco A -- Saito, Nobuhito -- Aburatani, Hiroyuki -- Mukasa, Akitake -- Berger, Mitchel S -- Chang, Susan M -- Taylor, Barry S -- Costello, Joseph F -- 1T32CA15102201/CA/NCI NIH HHS/ -- K08 NS079485/NS/NINDS NIH HHS/ -- K08NS079485/NS/NINDS NIH HHS/ -- P01CA81403/CA/NCI NIH HHS/ -- P30 CA082103/CA/NCI NIH HHS/ -- P30CA82103/CA/NCI NIH HHS/ -- P50 CA097257/CA/NCI NIH HHS/ -- P50CA097257/CA/NCI NIH HHS/ -- R01 CA163336/CA/NCI NIH HHS/ -- R01 CA169316/CA/NCI NIH HHS/ -- R01CA163336/CA/NCI NIH HHS/ -- R01CA169316-01/CA/NCI NIH HHS/ -- R25NS070680/NS/NINDS NIH HHS/ -- T32 CA128583/CA/NCI NIH HHS/ -- T32GM008568/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Jan 10;343(6167):189-93. doi: 10.1126/science.1239947. Epub 2013 Dec 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurological Surgery, University of California, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24336570" target="_blank"〉PubMed〈/a〉
    Keywords: Antineoplastic Agents, Alkylating/*adverse effects/therapeutic use ; Brain/drug effects/pathology ; Brain Neoplasms/*drug therapy/genetics/*pathology ; DNA Helicases/genetics ; DNA Mutational Analysis ; Dacarbazine/adverse effects/*analogs & derivatives/therapeutic use ; Glioma/*drug therapy/genetics/*pathology ; Humans ; Mutagenesis/drug effects ; Neoplasm Grading ; Neoplasm Recurrence, Local/*chemically induced/drug therapy/*genetics ; Nuclear Proteins/genetics ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins c-akt/genetics ; TOR Serine-Threonine Kinases/genetics ; Transcription Factors/genetics ; Tumor Suppressor Protein p53/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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